Diisopropylethylamine → 3-cyano-N-[2-(4-cyanophenyl)-4-hydroxybutyl]-N-methyl-1-naphthamide

HRID 749448Notes

Reaction equation

HRID 749448 reaction equation
[OH:1][CH2:2][CH2:3][CH:4]([C:8]1[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[CH:10][CH:9]=1)[CH2:5][NH:6][CH3:7].CCN(C(C)C)C(C)C.[C:25]([C:27]1[CH:28]=[C:29]([C:37](Cl)=[O:38])[C:30]2[C:35]([CH:36]=1)=[CH:34][CH:33]=[CH:32][CH:31]=2)#[N:26]>C(Cl)Cl>[C:25]([C:27]1[CH:28]=[C:29]([C:37]([N:6]([CH2:5][CH:4]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[CH:10][CH:9]=2)[CH2:3][CH2:2][OH:1])[CH3:7])=[O:38])[C:30]2[C:35]([CH:36]=1)=[CH:34][CH:33]=[CH:32][CH:31]=2)#[N:26]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 226366863-Cyano-1-naphthoyl chlorideHCID 689779184-{3-Hydroxy-1-[(methylamino)methyl]propyl}benzonitrile

Product 1

HCID 689764513-cyano-N-[2-(4-cyanophenyl)-4-hydroxybutyl]-N-methyl-1-naphthamideYield 67.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

4-{3-Hydroxy-1-[(methylamino)methyl]propyl}benzonitrile (0.55 g, 2.69 mmol) and DIPEA (0.77 g, 5.9 mmol) were dissolved in CH2Cl2 (5 mL). 3-Cyano-1-naphthoyl chloride (sse Method 11; 0.58 g, 2.69 mmol) was added in portions with stirring and cooling (external ice-bath). The mixture was stirred for 2 h with cooling and then diluted with CH2Cl2 (10 mL). The solution was washed twice with water, twice with a saturated aqueous KHSO4 solution and then with brine. The solvent was removed by evaporation and the residue flash chromatographed on silica gel (CH2Cl2-MeOH, 9:1). There was obtained 0.70 g (67%) of 3-cyano-N-[2-(4-cyanophenyl)-4-hydroxybutyl]-N-methyl-1-naphthamide as a white solid. 1H NMR (400 MHz, CDCl3): 1.4-2.5 (cm, 2H), 2.6 (s, 3H), 3.1-4.6 (cm, 6H), 6.4-7.8 (cm, 8H), 7.9 (d, 1H), 8.2 (s, 1H); LCMS: m/z 384 (M+1)+.

Workup

  1. temperaturecooling (external ice-bath)
  2. stirringThe mixture was stirred for 2 h
  3. temperaturewith cooling
  4. washThe solution was washed twice with water, twice with a saturated aqueous KHSO4 solution
  5. customThe solvent was removed by evaporation
  6. customthe residue flash chromatographed on silica gel (CH2Cl2-MeOH, 9:1)

Sources & evidence

ORD record
ord-f7314bd42de149bfb6f310fa3caf786c
Source dataset
uspto-grants-2008_07
Patent number
US07402581B2

Reaction notes

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